The long-term goal of our laboratory is to understand, through genetic analysis, the evolutionary forces producing new species and the attendant differences in their morphology and behavior. Here we propose to study two pair of species in the Drosophila melanogaster subgroup, one comprising a recently discovered evolutionary divergence D. santomea (a newly-found island endemic), and its sister species D. yakuba; and the other the independent sister pair D. mauritiana/D.simulans. We ask the following questions. 1. What are the forms and degrees of reproductive isolation between D. santomea and D. yakuba? We will quantify sexual, postzygotic, and "postmating, prezygotic" isolation. These studies are necessary for our genetic analysis of these traits, but will also allow us to compare this evolutionary divergence with two independent speciation events in the same group, all of which occurred at about the same time. 2. What are the genetic bases of sexual isolation, hybrid male sterility, and a striking difference in pigmentation between these two species? These questions will be answered with quantitative-trait-locus (QTL) mapping, a method more precise than the crude mutant-based mapping we have used in the past. The acquired information about the numbers, effects, and locations of chromosome regions affecting speciation and character differences will help answer long-standing questions of evolutionary genetics. 3. Does "reinforcement" operate in D. santomea/yakuba? These species have overlapping ranges on the island of Sao Tome, allowing us to perform a rare test for "reinforcement": the controversial idea that natural selection can increase the degree of sexual isolation between species in their area of overlap. 4. What is the genetic basis of sexual isolation between D. simulans and D. mauritiana? Almost nothing is known about the genetics of sexual isolation in this pair, whose divergence also involved island colonization. QTL mapping will reveal the numbers, effects, and locations of chromosomes regions involved in sexual isolation of males, of females, and of shortened interspecific copulation inhibiting gene flow. Our results will allow us to compare patterns of speciation in independent but closely related taxa, may eventually facilitate the location and isolation of "speciation" and "adaptation" genes, and may be relevant to understanding the origin of species in other animal groups, including humans.